search
Back to results

Metabolic Impact Assessment of Tenofovir Disoproxil Fumarate on Non-HIV-1 Infected Healthy Adult Male Volunteers

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Tenofovir Disoproxil Fumarate
Tenofovir DF placebo
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV-1, tenofovir DF

Eligibility Criteria

18 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Subjects must have documented negative HIV serology by ELISA and P24 antigen. This will be done at the screening visit.
  • Subjects must be clinically well males aged between 18 to 55 years.
  • Adequate renal function:
  • Calculated creatinine clearance (CrCl) >= 100 mL/min according to the Cockcroft Gault formula: Male: [(140 - age in years) x (actual body wt in kg)]/[72 x (serum creatinine in mg/dL)]= CrCl (mL/min)
  • Fasting blood glucose, total cholesterol and triglycerides within normal limits
  • Hepatic transaminases (AST and ALT) <= 3 x upper limit of normal (ULN)
  • Total bilirubin <= 1.5 mg/dL
  • Adequate hematologic function (absolute neutrophil count >= 1,000/mm3; platelets >= 50,000/mm3; hemoglobin >= 8.0 g/dL)
  • Serum amylase <= 1.5 x ULN (subjects with serum amylase > 1.5 x ULN will remain eligible if pancreatic lipase is <= 1.5 x ULN)
  • Serum phosphorus >= 2.2 mg/dL
  • Sexually active males must use condoms
  • Life expectancy >= 1 year
  • The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures

Exclusion Criteria:

  • Subjects with a waist hip ratio > 0.97 or BMI > 28 kg/m2 will be excluded
  • Acute or chronic hepatitis B infection (determined by positive hepatitis B surface antigen result at the screening visit)
  • Acute or chronic hepatitis C infection (determined by positive hepatitis C antibody result at the screening visit)
  • Other metabolic syndrome or disease process likely to cause marked disturbance in glucose and lipid homeostasis
  • Receiving on-going therapy with any of the following:
  • Metabolically active medications

  • Any lipid-lowering medication

    • Hormonal agents (oestrogens or androgens)
    • Glucocorticoids
    • Beta-blockers
    • Thiazide diuretics
    • Thyroid preparations
    • Psychotropic agents
    • Anabolic steroids
    • Megoestrol acetate

    • Nephrotoxic agents

      • aminoglycoside antibiotics
      • IV amphotericin B
      • cidofovir
      • cisplatin
      • foscarnet
      • IV pentamidine
      • other agents with significant nephrotoxic potential
    • Vancomycin
    • Oral or IV ganciclovir

    • Agents that inhibit or compete for elimination via active renal tubular secretion

      ** Probenecid

    • Systemic chemotherapeutic agents (i.e., cancer treatment medications)
    • Systemic corticosteroids
    • Interleukin 2 (IL 2) and other immunomodulating agents
    • Investigational agents

Administration of any of the above medications must be discontinued at least 30 days prior to the baseline visit and for the duration of the study period.

  • Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication.
  • Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance.
  • Malignancy or basal cell carcinoma.
  • Active, serious infections requiring parenteral antibiotic therapy within 15 days prior to screening.
  • Prior history of significant renal or bone disease.
  • Subjects should avoid giving blood for the duration of this study.
  • Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.

Sites / Locations

  • Chelsea and Westminster Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Group 1

Group 2

Arm Description

Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the first 14 days of the study. Tenofovir DF placebo tablet QD for the last 14 days of the study.

Tenofovir DF placebo tablet QD for the first 14 days of the study. Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the last 14 days of the study.

Outcomes

Primary Outcome Measures

To assess the impact on insulin sensitivity (determined by peripheral glucose uptake suing a euglycaemic clamp) of the administration of tenofovir DF compared with placebo for two weeks in HIV-1 seronegative healthy male volunteers.

Secondary Outcome Measures

To assess endothelial function by monitoring changes in Selectin P/E and PAI-1 assays.
To monitor adipocytokines by assessing adiponectin and leptin levels.
To monitor lipids by assessing large and small lipoprotein sub-fractions of HDL and LDL cholesterol, triglycerides, and non esterified fatty acid concentrations.

Full Information

First Posted
March 27, 2008
Last Updated
March 31, 2008
Sponsor
Gilead Sciences
search

1. Study Identification

Unique Protocol Identification Number
NCT00648817
Brief Title
Metabolic Impact Assessment of Tenofovir Disoproxil Fumarate on Non-HIV-1 Infected Healthy Adult Male Volunteers
Official Title
A Phase IV, Randomized, Double-Blind, Placebo-Controlled, Two-Phase Crossover Study of the Metabolic Impact of Tenofovir Disoproxil Fumarate on HIV-1 Seronegative Healthy Adult Males
Study Type
Interventional

2. Study Status

Record Verification Date
March 2008
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Metabolic changes commonly occur in HIV therapy. The purpose of this study is to assess the impact on insulin sensitivity from the administration of tenofovir disoproxil fumarate 300 mg compared with placebo in non-HIV-1 infected healthy adult males. Additionally, endothelial function, adipocytokines and lipids will be monitored.
Detailed Description
Double-blind, randomized, placebo-controlled study using a two-sequence two-period crossover structure. Sixteen HIV-1-negative males will be randomized 1:1 to one of two treatment arms. Group 1: Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the first 14 days of the study. Tenofovir DF placebo tablet QD for the last 14 days of the study. Group 2: Tenofovir DF placebo tablet QD for the first 14 days of the study. Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the last 14 days of the study. Physical examinations and laboratory analyses are conducted at screening, baseline, Day 14, and Day 28. A euglycaemic clamp protocol and an ECG are performed at the baseline, Day 14 and Day 28 visits. The primary efficacy endpoint of this study is insulin-mediated glucose disposal during a hyperinsulinaemic euglycaemic clamp study. Endothelial function will be monitored by Selectin P/E and PAI-1 levels; adipocytokine levels will be monitored by measuring adiponectin and leptin levels; and lipid subfractions, including cholesterol (large and small subfractions of HDL and LDL) triglycerides and non-esterified fatty acids will be measured. Safety will be evaluated by adverse event and clinical laboratory test reporting.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV-1, tenofovir DF

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
Placebo Comparator
Arm Description
Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the first 14 days of the study. Tenofovir DF placebo tablet QD for the last 14 days of the study.
Arm Title
Group 2
Arm Type
Active Comparator
Arm Description
Tenofovir DF placebo tablet QD for the first 14 days of the study. Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil) for the last 14 days of the study.
Intervention Type
Drug
Intervention Name(s)
Tenofovir Disoproxil Fumarate
Intervention Description
Tenofovir DF 300 mg QD (equivalent to 245 mg of tenofovir disoproxil)
Intervention Type
Drug
Intervention Name(s)
Tenofovir DF placebo
Intervention Description
Tenofovir DF placebo tablet QD
Primary Outcome Measure Information:
Title
To assess the impact on insulin sensitivity (determined by peripheral glucose uptake suing a euglycaemic clamp) of the administration of tenofovir DF compared with placebo for two weeks in HIV-1 seronegative healthy male volunteers.
Secondary Outcome Measure Information:
Title
To assess endothelial function by monitoring changes in Selectin P/E and PAI-1 assays.
Title
To monitor adipocytokines by assessing adiponectin and leptin levels.
Title
To monitor lipids by assessing large and small lipoprotein sub-fractions of HDL and LDL cholesterol, triglycerides, and non esterified fatty acid concentrations.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Subjects must have documented negative HIV serology by ELISA and P24 antigen. This will be done at the screening visit. Subjects must be clinically well males aged between 18 to 55 years. Adequate renal function: Calculated creatinine clearance (CrCl) >= 100 mL/min according to the Cockcroft Gault formula: Male: [(140 - age in years) x (actual body wt in kg)]/[72 x (serum creatinine in mg/dL)]= CrCl (mL/min) Fasting blood glucose, total cholesterol and triglycerides within normal limits Hepatic transaminases (AST and ALT) <= 3 x upper limit of normal (ULN) Total bilirubin <= 1.5 mg/dL Adequate hematologic function (absolute neutrophil count >= 1,000/mm3; platelets >= 50,000/mm3; hemoglobin >= 8.0 g/dL) Serum amylase <= 1.5 x ULN (subjects with serum amylase > 1.5 x ULN will remain eligible if pancreatic lipase is <= 1.5 x ULN) Serum phosphorus >= 2.2 mg/dL Sexually active males must use condoms Life expectancy >= 1 year The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures Exclusion Criteria: Subjects with a waist hip ratio > 0.97 or BMI > 28 kg/m2 will be excluded Acute or chronic hepatitis B infection (determined by positive hepatitis B surface antigen result at the screening visit) Acute or chronic hepatitis C infection (determined by positive hepatitis C antibody result at the screening visit) Other metabolic syndrome or disease process likely to cause marked disturbance in glucose and lipid homeostasis Receiving on-going therapy with any of the following: Metabolically active medications Any lipid-lowering medication Hormonal agents (oestrogens or androgens) Glucocorticoids Beta-blockers Thiazide diuretics Thyroid preparations Psychotropic agents Anabolic steroids Megoestrol acetate Nephrotoxic agents aminoglycoside antibiotics IV amphotericin B cidofovir cisplatin foscarnet IV pentamidine other agents with significant nephrotoxic potential Vancomycin Oral or IV ganciclovir Agents that inhibit or compete for elimination via active renal tubular secretion ** Probenecid Systemic chemotherapeutic agents (i.e., cancer treatment medications) Systemic corticosteroids Interleukin 2 (IL 2) and other immunomodulating agents Investigational agents Administration of any of the above medications must be discontinued at least 30 days prior to the baseline visit and for the duration of the study period. Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication. Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance. Malignancy or basal cell carcinoma. Active, serious infections requiring parenteral antibiotic therapy within 15 days prior to screening. Prior history of significant renal or bone disease. Subjects should avoid giving blood for the duration of this study. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Graeme Moyle, MD, MB, BS, DipGUM
Organizational Affiliation
Chelsea and Westminster Hospital, London, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chelsea and Westminster Hospital
City
London
ZIP/Postal Code
SW10 9NH
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Metabolic Impact Assessment of Tenofovir Disoproxil Fumarate on Non-HIV-1 Infected Healthy Adult Male Volunteers

We'll reach out to this number within 24 hrs